DESCRIPTION: The objective of this project is to develop an efficient and scalable organoid culture platform using core-shell decoupled hydrogel microcapsules. Organoids, organ-mimicking multicellular structures derived from pluripotent stem cells or organ progenitors, have recently emerged as an important system for both studies of fundamental stem cell biology and development of potential therapeutics. Research groups worldwide have made important progress in deriving organoids for various organs; however large-scale culture or production of organoids, a prerequisite for their industrial and clinical applications, has remained a challenge. Current organoid culture systems by embedding the stem or progenitor cells in bulk extracellular matrix (ECM) hydrogels have limited surface area for mass transfer and are not suitable for large-scale productions. We propose to develop a microcapsule-based, scalable organoid culture platform. The microcapsules have a core-shell structure where the core consists of ECM that supports the growth of the organoids and the shell forms robust spherical microcapsules, enabling suspension culture in stirred bioreactors. Compared with conventional culture in bulk ECM hydrogels, the microcapsules have a much higher surface-to-volume ratio for mass transfer and can be produced continuously at a large rate (>10,000/min) by a two-fluidic electrostatic cospraying. The anticipated outcome of this research is the development of a new organoid culture method that will not only facilitate the studies currently performed in numerous research groups but also accelerate and contribute to the translation of organoid technologies.